Takayasu Arteritis-related Pulmonary Hypertension Cohort And Interventional Therapy Study

1.The multicenter cohort study of pulmonary Takayasu's arteritis associated pulmonary hypertension[Background]Pulmonary Takayasu's arteritis associated pulmonary hypertension(PTA-PH)is one of the vascular complications of Takayasu's arteritis.PTA-PH is a relatively rare type of pulmonary vascular disease.The absence of specific clinical manifestation in patients with PTA-PH has led to delayed diagnosis or misdiagnosis,and subsequent poor prognosis.Currently,there is a paucity of data regarding the clinical characteristics,therapeutic drugs,and long-term outcomes of patients with PTA-PH.[Objectives]To describe the demographic,hemodynamic and imaging characteristics of patients with PTA-PH,and to explore the long-term survival outcome and prognostic factors in these patients.[Methods]We conducted a multi-center cohort study including patients with PTA-PH diagnosed at 13 referral centers between Jan.2007 and Jan.2019 in China.Patients with pulmonary artery involvement,should further fulfilled the diagnostic criteria of Takayasu's arteritis(modified Ishikawa criteria or 1990 American College of Rheumatology[ACR]criteria).Pulmonary artery involvement was determined by transcatheter pulmonary angiography or CT pulmonary angiography,and the diagnosis of pulmonary hypertension(PH)was based on the mean pulmonary artery pressure(mPAP)?25 mmHg measured by right heart catheterization.All patients were followed up to October 31,2019.The primary outcome was all-cause death events occurring during follow-up.Kaplan-Meier survival curve was employed to calculate survival probability.Multivariable Cox proportional hazards models were adopted to assess clinical variables associated with all-cause death.Multiple imputation method was used for imputation of missing data,and sensitivity analysis was performed based on full data set.[Results]A total of 140 patients with PTA-PH were included,with a female predominance(n=113,81%).The mean age at onset of symptoms and diagnosis of PTA-PH were respectively 36.1±14.3 years and 41.4±14.3 years,yielding a median diagnostic delay of 2 years.The most common clinical symptom was exertional dyspnea(n=127,91%),followed by hemoptysis(n=50,36%).The median of six minute walking distance was 400(308-456)m.Seventy-three patients(52%)were in WHO function class III-IV at diagnosis.The median of mPAP was 48(38-59)mmHg,and pulmonary vascular resistance 9.4(5.7-14.0)Wood U.In terms of treatments,86(61%)patients were treated by glucocorticoids,29(21%)by immunosuppressive agents,and 127(91%)by targeted agents for PH.Most of the patients with PTA-PH(n=118,84%)had bilateral pulmonary artery involvement.Pulmonary lobar arteries(n=125,96%)were the most frequently affected sites.Luminal stenosis(n=134,96%)or occlusion(n=104,75%)was the main imaging type.Pre-capillary PH was present in 118 patients(84%)and combined post-and pre-capallary PH in 14 patients(10%).Moreover,isolated post-capillary PH was not observed on the basis of available data.Compared with patients with pre-capillary PH,those with combined PH had a longer diagnostic delay(8.0 years vs.2.0 years,p=0.045),a higher mPAP(61 mmHg vs.48 mmHg,p=0.030)and a mean right atrial pressure(20 mmHg vs.7 mmHg,p<0.001).Eighty-one(58%)patients had normal levels of inflammatory markers at diagnosis.These patients had a higher mPAP(50 mm Hg vs.45 mm Hg,p=0.008)than patients with elevated inflammatory markers level.The median time of first clinical follow-up was 6(3-15)months.In a subset of 92 patients who completed first clinical assessments,significant improvements have been found in N-terminal pro-brain natriuretic peptide(NT-proBNP),cardiac index,and pulmonary vascular resistance after targeted therapies for PH.During a median follow-up time of 24(9-56)months,all-cause death was recorded in 20 patients.The main cause of death was right heart failure(n=17).The 1-year,3-year and 5-year survival rates in patients with PTA-PH were 94.0%,83.2%and 77.2%,respectively.A backward stepwise multiple Cox regression model was used to find that the presence of syncope(adjusted hazard ratio[HR]:5.38,95%confidence interval[CI]:1.77-16.34;p=0.003),NT-proBNP level(adjusted HR:1.04[per 100 pg/ml],95%CI:1.03-1.06;p<0.001)and mean right atrial pressure(adjusted HR:1.07[per 1 mmHg],95%CI:1.01-1.13;p=0.015)were significantly associated with an increased risk of all-cause mortality.[Conclusions](1)PTA-PH dominantly affects young women,with the notably clinical symptoms for exertional dyspnea and hemoptysis.The hemodynamics was severely compromised at diagnosis.(2)Pulmonary artery involvement is an important cause of PH development in patients with PTA-PH.Moreover,some patients presented with combined PH.Lobar artery is the most common involved vessel.Luminal stenosis or occlusion is the main imaging type.(3)The 5-year survival rate of patients with PTA-PH was 77.2%.The presence of syncope,NT-proBNP level and mean right atrial pressure can effectively predict the all-cause mortality.2.Percutaneous transluminal pulmonary angioplasty for pulmonary Takayasu's arteritis associated pulmonary hypertension[Background]Percutaneous transluminal pulmonary angioplasty(PTPA),an interventional technique using balloon to dilate stenotic pulmonary vessels,has been widely used in patients with chronic thromboembolic pulmonary hypertension(CTEPH)in recent years.PTPA can effectively improve pulmonary stenosis,reduce pulmonary artery pressure and pulmonary vascular resistance in patients with CTEPH.However,the efficacy and safety of this technique for treating pulmonary arteriopathy in patients with pulmonary Takayasu's arteritis associated pulmonary hypertension(PTA-PH)remains to be investigated.[Objectives]The aims of this study are to explore the efficacy and safety of PTPA in patients with PTA-PH,and analyze predictors of achieving a treatment response to PTPA.Moreover,we also evaluated the incidence of restenosis after treatment and long-term survival outcome of these patients.[Methods]From Jan.2016 to Dec.2019,this single center,prospective cohort enrolled 90 patients with PTA-PH.Of which,50 patients were treated by PTPA while 40 were prescribed with drug treatment alone.The effectiveness endpoints of PTPA were the improvements of hemodynamic and cardiac function parameters after treatment,and the safety endpoints were perioperative complications and death.All patients underwent repeated right heart catheterization and pulmonary arteriography for at least 3 months after PTPA,thereafter followed by regular assessments every 3 months.The PTPA treatment response was defined as a decrease of pulmonary vascular resistance more than 30%in comparision to baseline.Multivariable logistic regression was used to assess the associations of baseline factors with PTPA treatment response,and variables selection was based on the least absolute shrinkage versus selection operator model(LASSO).The Kaplan-Meier analysis was used to calculate survival probability,with log-rank test for comparisons of survival curves between different groups.Multivariate Cox proportional hazards model was employed to evaluate the effect of PTPA treatment on the prognosis of patients with PTA-PH.[Results]A total of 150 PTPA sessions were performed for 360 pulmonary vascular lesions in 50 patients with PTA-PH,along with 14 stents implanted in the proximal lesions of 10 patients.The median hemodynamic follow-up time was 7(5-9)months.Patients treated by PTPA showed significant improvements in mean pulmonary artery pressure(median,48 mmHg to 37 mmHg,p<0.001),pulmonary vascular resistance(median,9.6 Wood U to 4.8 Wood U,p<0.001),and cardiac output(median,4.2 L/min to 6.1 L/min,p=0.016),in comparison to baseline.The WHO function class(?-?/?-?:26/24 vs.43/7,p<0.001),six minute walk distance(412 m vs.492 m,p<0.001),and N-terminal pro-brain natriuretic peptide level(704 pg/mL vs.148 pg/mL,p<0.001)were also significantly improved.Restenosis occurred in 5(1.4%)lesions of 4(8%)patients during follow-up,including 3 in-stent restenosis.The most common perioperative complication was pulmonary artery injury(27/150,18%).The incidence of postoperative reperfusion pulmonary edema was 4%(n=6),but no perioperative death was observed.Thirty-five(70%)patients achieved a treatment response to PTPA.A multivariate logistic model based on LASSO regression found that cardiac output was the only baseline variable that could predict PTPA treatment response(Odds ration:0.26,95%confidence interval:0.07-0.98;p=0.046).Patients with low cardiac output are more likely to benefit from PTPA.During a median follow-up of 39(26-54)months,three patients died.Kaplan-Meier survival analysis found that patients treated by PTPA had a significantly improved prognosis than those did not(log-rank p=0.008).After adjusting for demographic information,clinical variables and treatment drugs,PTPA is still an important predictor of prognosis improvement in patients with PTA-PH.[Conclusions](1)PTPA treatment could effectively improve the pulmonary hemodynamics and cardiac function in patients with PTA-PH,with an acceptable safety profiles.The overall incidence of restenosis was low,but a high risk of in-stent restenosis remained.(2)Cardiac output was an independent predictor of achieving a treatment response to PTPA.(3)Compared drugs alone during the same period,PTPA significantly improved long-term survival of patients with PTA-PH.